On November 13, 2020, the FDA accelerated the approval of pembrolizumab (Keytruda; Merck), a PD-1 inhibitor, plus chemotherapy, for the treatment of locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) in patients with PD-L1 (combined positive score [CPS] ≥10), as determined by an FDA-approved test.
The FDA accelerated this approval based on the KEYNOTE-355 study, a multicenter, randomized, double-blind, phase 3 study of 847 patients with locally recurrent unresectable or metastatic TNBC. The patients had not received chemotherapy in the metastatic setting and were randomized to pembrolizumab plus chemotherapy versus chemotherapy and placebo.
The main efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review according to Response Evaluation Criteria in Solid Tumours criteria version 1.1, which was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ in the subgroup of patients with tumors expressing PD-L1 (CPS ≥10). Additional efficacy outcome measures included overall survival, objective response rate (ORR), and duration of response (DOR) as assessed by blinded independent central review.
Pembrolizumab in combination with chemotherapy significantly reduced the risk for disease progression and death by 35% in the patients whose tumors expressed PD-L1 (CPS ≥10) versus with the same chemotherapy regimens alone (hazard ratio, 0.65; 95% confidence interval [CI], 0.49-0.86; P = .0012); the median PFS was 9.7 months (95% CI, 7.6-11.3) versus 5.6 months (95% CI, 5.3-7.5), respectively. Adverse events were observed in 136 (62%) of the 220 patients who received pembrolizumab plus chemotherapy versus 79 (77%) of the 103 patients who received chemotherapy alone. The ORRs were 53% and 40%, respectively, and the DOR was 19.3 months and 7.3 months, respectively, in the pembrolizumab plus chemotherapy group versus the chemotherapy-alone group.
“Approximately 15% to 20% of patients with breast cancer are diagnosed with triple-negative breast cancer, which is a difficult-to-treat and aggressive cancer,” said Hope S. Rugo, MD, FASCO, Director, Breast Oncology and Clinical Trials Education, University of California San Francisco.
Fatal adverse reactions occurred in 2.5% of patients who received pembrolizumab plus chemotherapy. The most common (≥20%) adverse events in the pembrolizumab arm were fatigue, nausea, alopecia, diarrhea, constipation, vomiting, rash, cough, decreased appetite, and headache.